近日，法国巴黎西岱大学的Benoit Ladoux及其研究小组与丹麦哥本哈根大学的Amin Doostmohammadi等人合作并取得一项新进展。经过不懈努力，他们发现动态力影响被清除细胞的存活命运。相关研究成果已于2025年1月8日在国际知名学术期刊《自然—物理学》上发表。

该研究团队黏附连接处的力传递改变会抑制凋亡细胞的清除。通过将具有不同水平E-钙黏蛋白连接的细胞实验与细胞单层的三维建模相结合，研究人员发现这些改变不仅影响挤出细胞的命运，还会使挤出过程从顶端转向基底侧，从而导致细胞侵入柔软的胶原凝胶。

研究人员利用来源于乳腺癌患者的在基质胶中培养的异种移植瘤和囊肿，对他们的发现进行了泛化验证。这项研究结果将细胞间通信调节的细胞间力传递与细胞挤出机制联系起来，这对形态发生和癌细胞侵袭过程具有潜在意义。

据悉，组织通过细胞挤出过程消除不适应、不需要或不必要的细胞，这一过程可能导致凋亡细胞和活细胞均被清除。然而，影响挤出细胞命运的力学特征尚不清楚。

附：英文原文

Title: Dynamic forces shape the survival fate of eliminated cells

Author: Balasubramaniam, Lakshmi, Monfared, Siavash, Ardaeva, Aleksandra, Rosse, Carine, Schoenit, Andreas, Dang, Tien, Maric, Chrystelle, Hautefeuille, Mathieu, Kocgozlu, Leyla, Chilupuri, Ranjith, Dubey, Sushil, Marangoni, Elisabetta, Doss, Bryant L., Chavrier, Philippe, Mge, Ren-Marc, Doostmohammadi, Amin, Ladoux, Benoit

Issue&Volume: 2025-01-08

Abstract: Tissues eliminate unfit, unwanted or unnecessary cells through cell extrusion, and this can lead to the elimination of both apoptotic and live cells. However, the mechanical signatures that influence the fate of extruding cells remain unknown. Here we show that modified force transmission across adherens junctions inhibits apoptotic cell eliminations. By combining cell experiments with varying levels of E-cadherin junctions and three-dimensional modelling of cell monolayers, we find that these changes not only affect the fate of the extruded cells but also shift extrusion from the apical to the basal side, leading to cell invasion into soft collagen gels. We generalize our findings using xenografts and cysts cultured in matrigel, derived from patients with breast cancer. Our results link intercellular force transmission regulated by cell–cell communication to cell extrusion mechanisms, with potential implications during morphogenesis and invasion of cancer cells.

DOI: 10.1038/s41567-024-02716-5

Source: https://www.nature.com/articles/s41567-024-02716-5